Nerve growth factor (NGF) is synthesized and secreted by two cell lines derived from the nervous system, the rat C6 glioma and the mouse NB2a neuroblastoma. The content of the NGF is increased in either cell line by agents which elevate cyclic AMP, Beta-adrenergic receptor agonists for the glioma cells and prostaglandin E1 or adenosine for the neuroblastoma. The increase in NGF content follows an elevation of cyclic AMP content and the concomitant activation of protein kinase. The increase in cyclic AMP does not depend on an increase in the net synthesis of NGF, but rather appears to derive from an activation of a peptidase which may form NGF from a pro NGF. Research is being carried out to determine 1) the characteristics of the glioma cell protein kinase(s); 2) the precise mechanism by which protein kinase activates the peptidase and 3) the biochemical characteristics of the precursor NGF.